The invention relates generally to microfluidic systems and to methods for loading microfluidic chips in such systems.
Electrophoretic separation of biomolecules is very important in modern biology and biotechnology applications such as DNA sequencing, protein molecular weight determination and genetic mapping. Electrophoresis is a process by which individual molecular species are separated in a conductive medium (such as a liquid solution or a cross-linked polymer) by applying an electric field. The charged molecules migrate through the solution and separate into distinct bands due to their mobility difference through the media. The rates are influenced by factors such as a viscosity of the solution, a mass and charge of the molecules, and a strength and duration of the electric field.
An increase in a voltage gradient (V/cm) applied to the electrophoretic device results in a corresponding decrease in the time needed to perform the separation. However, increasing the voltage gradient is governed by certain constraints. For example, increasing the voltage gradient beyond a certain point may result in an increase in joule heating which would in turn alter the properties of the medium in which the molecules are being separated. The change of the medium properties leads to an increase in sample diffusion and thus degraded the separation resolution. In order to overcome the above limitations, electrophoresis can be performed in a capillary or miniaturized channel. The large surface-area-to-volume ratio of the electrophoretic devices offers efficient dissipation of Joule heat, allowing higher electric field to be used, thus resulting in the shorter analysis time and better separation efficiency.
Microchips are small microfluidic devices that perform chemical and physical operations such as capillary electrophoresis with microscale sample volumes. These devices often have the benefits of fast reactions, rapid detection, small reagent consumption, ease of automation and simple transfer between reaction vessels. Microfluidic devices are commonly referred to as “lab-on-a-chip.”
In microchip electrophoresis, a sample is loaded in a sample reservoir and a voltage is applied between a sample reservoir and a waste reservoir to move sample into the loading channel. However, proteins with different mobilities may be separated during this loading process, resulting in a biased injection, in which the sample injected into the separation channel does not represent the original sample composition.
Therefore, there is a need for a microfluidic device that provides sample-loading techniques where the sample composition is uniform at the injection point.